Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes

Phase 4

Brief Summary: Tuberculosis (TB) is a leading cause of death in HIV-infected individuals. There are insufficient data correlating concentrations of anti-TB drugs with treatment response. We hypothesize that sub-therapeutic concentrations of anti-TB drugs are associated with inadequate TB treatment response to Mycobacterium tuberculosis.

Detailed Description: During the study periodic monitoring will be conducted to ensure that the protocol and Good Clinical Practices (GCPs) are being followed.The monitors may review source documents to confirm that the data recorded on CRFs is accurate. The study site may be subject to review by the Institutional Review Board (IRB) and/or appropriate regulatory authorities.

A CRF will be completed for each included subject and will be signed by the investigator or by an authorized staff member to attest that the data is true. Any corrections to entries made in the CRFs, source documents must be dated, initialed and explained (if necessary) and should not obscure the original entry. Qualit assurance will as also be performed regularly on the CRFs.

The primary end point will be analyzed using Time to event (cure, death, relapse etc)analysis and failure rates and hazard ratios will be calculated accordig to categorical drug concentrations with proposed cutt offs.

Secondary end points will be analysed using time to event for occurence of toxicities which will also be corelated to the drug concentrations.

Recruitment & Eligibility

Inclusion Criteria

Evidence of a personally signed and dated informed consent
Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Age of ≥18 years
First episode of pulmonary TB i.e. proven or highly suspected TB considered for TB treatment qualifying for 6 months anti-Tb drugs regimen
Confirmed HIV-1 infection

Exclusion Criteria

Unable to provide informed consent
Documented or highly suspected TB infection of any organs/systems other than the lung requiring TB treatment longer than 6 months
Previously treated for a mycobacterial infection (TB or atypical mycobacterial infection, active or latent)
Pregnancy or planned pregnancy within the next year
Unwillingness to perform pregnancy test
Decompensated liver disease and/or aminotransferases >5x ULN
GFR < 50 ml/min
Co-morbidities reducing life expectancy to <1 year (e.g. cancer)
Patient wishes to take part in another interventional study

Arm && Interventions

Group	Intervention	Description
anti-tuberculosis drugs	Rifampicin, Isoniazid, Ethambutol, Pyrazinamide	Rifampicin, Isoniazid, Ethambutol, Pyrazinamide tablets 3 to 5 tablets once daily for 2 months followed by Rifampicin, Isoniazid 3 to 5 tablets once daily for 4 months

Primary Outcome Measures

Name	Time	Method
clinical outcome	At the end of treatment (6 months after enrolmet)	To investigate the association between serum concentrations of antituberculosis drugs and tuberculosis treatment response in HIV-TB-co-infected individuals.

Secondary Outcome Measures

Name	Time	Method
Cmax	At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation	To investigate the steady-state pharmacokinetic parameters of anti-TB drugs at different time-points over the course of TB-treatment
Number of adverse events	2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation	To assess the safety and tolerability of anti-TB drugs based on the WHO guidelines
ART trough levels	At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation	To correlate the effect of anti-TB drugs on plasma concentrations of efavirenz or protease inhibitors and vice versa.
Isoniazid Cmax	At 2 weeks, 8 weeks and 24 weeks	To evaluate the effect of acetylator geno-and phenotype (NAT-2 gene) on isoniazid plasma concentrations and toxicity

Receive instant email notifications about changes in this clinical trial

Receive instant email notifications about changes in this clinical trial